Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos

Zhao, Xuesong; Ren, Xin; Zhu, Rong; Luo, Zhouying; Ren, Baixiang

doi:10.1016/j.aquatox.2016.09.013

Cited by 210 publications

(91 citation statements)

References 62 publications

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“…3A and B). However, ROS generation is also associated with mitochondria (22). Fluorescence probe DCFH-DA was used to determine the levels of ROS production in glucose-stimulated podocytes.…”

Section: Sirt4 Overexpression Inhibits Apoptosis Via the Mitochondriamentioning

confidence: 99%

SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis

Shi

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Diabetic nephropathy is a diabetic complication associated with capillary damage and increased mortality. Sirtuin 4 (SIRT4) plays an important role in mitochondrial function and the pathogenesis of metabolic diseases, including aging kidneys. The aim of the present study was to investigate the association between SIRT4 and diabetic nephropathy in a glucose-induced mouse podocyte model. A CCK-8 assay showed that glucose simulation significantly inhibited podocyte proliferation in a time-and concentration-dependent manner. Reverse transcription-quantitative polymerase chain reaction and western blot analysis showed that the mRNA and protein levels of SIRT4 were notably decreased in a concentration-dependent manner in glucose-simulated podocytes. However, SIRT4 overexpression increased proliferation and suppressed apoptosis, which was accompanied by increases in mitochondrial membrane potential and reduced production of reactive oxygen species (ROS). Notably, SIRT4 overexpression downregulated the expression of apoptosis-related proteins NOX1, Bax and phosphorylated p38 and upregulated the expression of Bcl-2 in glucose-simulated podocytes. In addition, SIRT4 overexpression significantly attenuated the inflammatory response, indicated by reductions in the levels of TNF-α, IL-1β and IL-6. These results demonstrate for the first time that the overexpression of SIRT4 prevents glucose-induced podocyte apoptosis and ROS production and suggest that podocyte apoptosis represents an early pathological mechanism leading to diabetic nephropathy.

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Section: Sirt4 Overexpression Inhibits Apoptosis Via the Mitochondriamentioning

confidence: 99%

SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis

Shi

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…Finally, ROS formation as a result of Ag and ZnO NPs exposure can cause a change in cell function and cellular lipid peroxidation resulting in the enhancement of ROS production while simultaneously quenching naturally occurring antioxidants (Premanathan et al 2011, Adeyemi and Faniyan 2014, Zhao et al 2016, Zhu et al 2016. This triggers an inflammatory response and induces DNA damage within the cell and ultimately resulting in cell death (Nel et al 2006, Yu et al 2013, Murphy et al 2015b, Saini et al 2016.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of cell death caused by NPs has been attributed to oxidative stress, with ROS generation indicated as a primary mechanism of NP related apoptotic cell death (Sastre et al 2000, Piao et al 2011, Yu et al 2013, Murphy et al 2015a, Saini et al 2016, Zhao et al 2016, Zhu et al 2016. ROS generation in the cells is regulated by protective enzymes and antioxidant mechanisms.…”

Section: Discussionmentioning

confidence: 99%

In vitro comparative cytotoxicity study of aminated polystyrene, zinc oxide and silver nanoparticles on a cervical cancer cell line

Sharma

Gorey²,

Casey

2018

Drug and Chemical Toxicology

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Nanoparticles use in nano-biotechnology applications have increased significantly with Aminated polystyrene amine (AmPs NP), Zinc oxide (ZnO NP), and Silver (Ag NP) nanoparticles utilized in wide variety of consumer products. This has presented a number of concerns due to their increased exposure risks and associated toxicity on living systems. Changes in the structural and physicochemical properties of nanoparticles can lead to changes in biological activities. This study investigates, compares, and contrasts the potential toxicity of AmPs, ZnO and Ag NPs on an in vitro model (HeLa cells) and assesses the associated mechanism for their corresponding cytotoxicity relative to the surface material. It was noted that NPs exposure attributed to the reduction in cell viability and high-level induction of oxidative stress. All three test particles were noted to induce ROS to varying degrees which is irrespective of the attached surface group. Cell cycle analysis indicated a G2/M phase cell arrest, with the corresponding reduction in G0/G1 and S phase cells resulting in caspase-mediated apoptotic cell death. These findings suggest that all three NPs resulted in the decrease in cell viability, increase intracellular ROS production, induce cell cycle arrest at the G2/M phase and finally result in cell death by caspase-mediated apoptosis, which is irrespective of their differences in physiochemical properties and attached surface groups.ARTICLE HISTORY

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“…29 Many NPs, including ZnO NPs, can trigger damage to mitochondria and increase the mitochondrial membrane potential. [30][31][32] In the present study, a ROS assay was used to evaluate the change of the ROS level in BV-2 cells after exposure to 50 nm ZnO NPs. The results indicated that the ZnO NP treatment …”

mentioning

confidence: 99%

Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

Wei

Wang

Chen

et al. 2017

IJN

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With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1 −/− BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity.

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Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos

Cited by 210 publications

References 62 publications

SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis

SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis

In vitro comparative cytotoxicity study of aminated polystyrene, zinc oxide and silver nanoparticles on a cervical cancer cell line

Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

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